Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster (HZ/su) Vaccine in Adults With Solid Tumours Receiving Chemotherapy

Browse trials for

• Herpes Simplex 305
• Herpes Zoster 360

Keywords

• ≥18 years of age
• Chemotherapy
• Solid tumours
• Immunogenicity
• Herpes Zoster
• Safety
• Shingles

Herpes Simplex

305 studies on the registry are indexed under Herpes Simplex; 31 are open to participants now.

This study's enrollment of 237 is above the median of 101 across 227 interventional studies indexed under Herpes Simplex.

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.

Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.

Study arms

• Experimental
  GSK1437173A Group

  Subjects received the first dose of GSK 1437173A at least 10 days (up to 1 month) before start of chemotherapy cycle or at the first day (allowing a window of +/- 1 day) of the first (or second) chemotherapy cycle. The second dose of GSK 1437173A vaccine was administered between 1 and 2 months after the first vaccination and at the first day (allowing a window of +/- 1 day) of a subsequent cycle of chemotherapy. The study products were administered intramuscularly into a deltoid muscle. The choice of and use of chemotherapy, or any other medication related to the patients' current conditions, were based on the local standard of care for the patients.

  Biological: GSK 1437173A

• Placebo comparator
  Placebo Group

  Subjects received the first dose of placebo at least 10 days (up to 1 month) before start of chemotherapy cycle or at the first day (allowing a window of +/- 1 day) of the first (or second) chemotherapy cycle. The second dose of placebo was administered between 1 and 2 months after the first vaccination and at the first day (allowing a window of +/- 1 day) of a subsequent cycle of chemotherapy. The study products were administered intramuscularly into a deltoid muscle. The choice of and use of chemotherapy, or any other medication related to the patients' current conditions, were based on the local standard of care for the patients.

  Drug: Placebo

Interventions

• BiologicalGSK 1437173A

  2 doses administered by intramuscular (IM) injection into the deltoid muscle of the non-dominant arm.

  Also known as: HZ/su, GSK Biologicals Herpes Zoster subunit (HZ/su) vaccine

• DrugPlacebo

  2 doses administered by IM injection into the deltoid muscle of the non-dominant arm.

Primary outcomes

1. Adjusted Geometric Means for Anti-glycoprotein E (gE) Antibodies in PreChemo Groups

   Adjusted geometric means (GMC) of GSK1437173A over placebo for anti-glycoprotein E (gE) antibody enzyme-linked immunosorbent assay (ELISA) concentrations in PreChemo Groups only.

   Time frame: At Month 2

2. Anti-Varicella Zoster Virus (VZV) gE Antibody Concentrations

   Antibody concentrations as determined by ELISA are presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL). The seropositivity cut-off value was greater than or equal to (≥) 97 mIU//mL.

   Time frame: At Month 2

3. Number of Subjects With Any and Grade 3 Solicited Local Symptoms

   Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal every day activities. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.

   Time frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses

4. Number of Days With Solicited Local Symptoms

   The number of days with any local symptoms has been assessed during the post-vaccination period.

   Time frame: During the 7-day (Days 0-6) post-vaccination period following each dose

5. Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

   Assessed solicited general symptoms were fatigue, gastrointestinal \[symptoms included nausea, vomiting, diarrhoea and/or abdominal pain\], headache, myalgia, shivering and fever \[defined as oral, axillary or tympanic temperature equal to or above 37.5 degrees Celsius (°C)\]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever \> 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.

   Time frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses

6. Number of Days With Solicited General Symptoms

   The number of days with any general symptoms has been assessed during the post-vaccination period.

   Time frame: During the 7-day (Days 0-6) post-vaccination period following each dose

7. Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)

   An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.

   Time frame: During the 30-day (Days 0-29) post-vaccination period

8. Number of Subjects With Serious Adverse Events (SAEs)

   Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Related SAE= SAE assessed by the investigator as causally related to the study vaccination.

   Time frame: From first dose up to 30 days post last vaccination

9. Number of Subjects With Any and Related Potential Immune Mediated Diseases (pIMDs)

   Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. Related = pIMDs assessed by the investigator as causally related to the study vaccination.

   Time frame: From first vaccination up to 30 days post last vaccination

Secondary outcomes

1. Anti-VZV gE Antibody Concentrations

   Antibody concentrations as determined by ELISA are presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL). The seropositivity cut-off value was greater than or equal to (≥) 97 mIU//mL.

   Time frame: At Months 0, 1, 6 and 13

2. Number of Subjects With Vaccine Responses for Anti-gE Antibody ELISA Concentrations

   Vaccine response defined as: For initially seronegative subjects, antibody concentration at post-vaccination ≥ 4 fold the cut-off for Anti-gE (4x97 mIU/ml); For initially seropositive subjects, antibody concentration at post-vaccination ≥ 4 fold the pre-vaccination antibody concentration.

   Time frame: At Months 1, 2, 6 and 13

3. Descriptive Statistics of the Frequency of gE-specific CD4[2+] T-cells in PreChemo Groups

   Descriptive statistics were tabulated for CD4\[2+\] cells, which are gE specific CD4+ T-cells with at least two activation markers (\[2+\]), expressed from the activation markers interferon-gamma (IFN-γ), interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α) and cluster of differentiation 40-ligand (CD40-L), as determined by intracellular cytokine staining (ICS) method.

   Time frame: At Months 0, 1, 2 and 13

4. Number of Subjects With Vaccine Responses for gE-specific CD4[2+] T-cells in PreChemo Groups

   Vaccine response defined as: For initially seronegative subjects with pre-vaccination T-cell frequencies below the threshold, at least a 2-fold increase as compared to the threshold (2x320 Events/10E6 CD4+ T cells); For initially seropositive subjects with pre-vaccination T-cell frequencies above the threshold, at least a 2-fold increase as compared to pre-vaccination T-cell frequencies.

   Time frame: At Months 1, 2 and 13

5. Number of Subjects With Serious Adverse Events (SAEs)

   SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Related SAE = SAE assessed by the investigator as causally related to the study vaccination.

   Time frame: From 30 days post last vaccination up to study end (Month 13)

6. Number of Subjects With Any Potential Immune Mediated Diseases (pIMDs)

   Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.

   Time frame: From 30 days post last vaccination up to study end (Month 13)

Baseline characteristics

Publications

• Vink P, Delgado Mingorance I, Maximiano Alonso C, Rubio-Viqueira B, Jung KH, Rodriguez Moreno JF, Grande E, Marrupe Gonzalez D, Lowndes S, Puente J, Kristeleit H, Farrugia D, McNeil SA, Campora L, Di Paolo E, El Idrissi M, Godeaux O, Lopez-Fauqued M, Salaun B, Heineman TC, Oostvogels L; Zoster-028 Study Group. Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in patients with solid tumors, vaccinated before or during chemotherapy: A randomized trial. Cancer. 2019 Apr 15;125(8):1301-1312. doi: 10.1002/cncr.31909. Epub 2019 Feb 1. Erratum In: Cancer. 2020 Jun 15;126(12):2941. doi: 10.1002/cncr.32842. PubMed 30707761 ↗

Related links

• Full CSR posting on gsk. ↗

Individual participant data

Plan to share: Yes — IPD for this study will be made available via the Clinical Study Data Request site.

Supporting information: Study protocol, Sap, Icf, Csr